Linolenic acid-modified MPEG-PEI micelles for encapsulation of amphotericin B

Future Med Chem. 2019 Oct;11(20):2647-2662. doi: 10.4155/fmc-2018-0580. Epub 2019 Oct 17.

Abstract

Aim: To encapsulate amphotericin B (AmB) with reduced toxicity and comparable activity. Results & methodology: The α-linolenic acid (ALA)-modified monomethoxy polyethylene glycol-g-PEI-g-ALA conjugate was employed to prepare AmB-loaded micelles (AmB-M). In vitro activity and release behavior of AmB-M were investigated. AmB-M enhanced AmB's water-solubility to 1.2 mg/ml, showing good storage stability. AmB-M could achieve a sustained and slow release of AmB, low hemolysis activity and negligible kidney toxicity when compared with commercial AmB injection. Antifungal activity and biofilm inhibition experiments confirmed that the antifungal activity of AmB-M against Candida albicans was similar to that of AmB injection. Conclusion: Monomethoxy polyethylene glycol-g-PEI-g-ALA micelles could be a preferable choice to treat systemic fungal infections as an efficient drug delivery system.

Keywords: amphotericin B; antifungal activity; monomethoxy polyethylene glycol; polyethylene imine; α-linolenic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphotericin B / adverse effects
  • Amphotericin B / chemistry*
  • Amphotericin B / pharmacology
  • Animals
  • Antifungal Agents / adverse effects
  • Antifungal Agents / chemistry*
  • Antifungal Agents / pharmacology
  • Biofilms / drug effects
  • Candida albicans / drug effects
  • Drug Compounding*
  • Hemolysis / drug effects
  • Humans
  • Micelles*
  • Microbial Sensitivity Tests
  • Polyethylene Glycols / chemistry*
  • alpha-Linolenic Acid / chemistry*

Substances

  • Antifungal Agents
  • Micelles
  • alpha-Linolenic Acid
  • Polyethylene Glycols
  • Amphotericin B